Endothelial cells in the adult mammal are among the least proliferative cell types, with about one in 10,000 cells entering the cell cycle at any given time. This quiescence is rapidly reversed in response to growth factors during pathological neovascularization, particularly during tumorigenesis. The robust proliferative switch of the quiescent endothelium is a complex process that is governed by a network of checks and balances. Small 22-nt RNAs called miRNAs are key regulators of several physiological processes, including angiogenesis.
The miR-103 microRNA precursor (homologous to miR-107), is a short non-coding RNA gene involved in gene regulation. miR-103 and miR-107 have now been predicted or experimentally confirmed in human. microRNAs are transcribed as approximately 70 nucleotide precursors and subsequently processed by the Dicer enzyme to give an approximately 22 nucleotide product. In this case the mature sequence comes from the 5′ arm of the precursor. The mature products are thought to have regulatory roles through complementarity to mRNA.
mir-103 and mir-107 were noted as being upregulated in obese mice and were subsequently found to have a key role in insulin sensitivity. This lead to a suggestion that these microRNAs represent potential targets for the treatment of type 2 diabetes. mir-103 has also been linked with chronic pain and intestinal cell proliferation.
Trex1 exonuclease degrades ssDNA to prevent chronic checkpoint activation and autoimmune disease. C-terminal truncations in human 3′-5′ DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. In Cerebroretinal Vasculopathy, less TREX1 results in less blood vessels; and the disease manifestations begin during the fourth or fifth decade and there is 100% mortality over a 5 to 10 year period.